These studies concern the structure of human plasma low-density-lipoproteins (LDL). They were initiated by our hypothesis that a structurally abnormal lipoprotein exists in the plasma of individuals with familial hyperlipemic diseases, as an expression of an altered genome. It has been shown that in a small group of individuals with hyper-pre-beta-lipoproteinemia, LDL exists as a family of macromolecules differing in molecular weight and amount of bound lipid. In normal and hyper-beta-lipoproteinemics there exists only a single species of LDL, but the molecular weight of this LDL differs from one individual to the next. One objective of our research is to expand the number of subjects studied in order to generalize on these observations. Is LDL heterogeneity a common feature of hyper-pre-beta-lipoproteinemia or do only a subpopulation of patients have this LDL defect? By studying LDL molecular weight in several families of normal and hyper-pre-beta-lipoproteinemics, we hope to determine if the molecular weight variability of LDL is an inherited state. The major thrust of our research, however, is towards the isolation and characterization of the protein moiety of LDL (apo-LDL). This water insoluble protein dissolves in concentrated formic acid and, using this solvent, it has been possible to study its physical and also its chemical properties. It is our plan to proceed with cleavage of the protein and a study of its peptide structure.